Reports regarding the ability to deliver mesenchymal stem cells (MSC) in vivo intravascularly to ischemically damaged kidneys can be found in the literature. Preclinical and clinical studies have demonstrated that adult stem cells may be recruited from the circulation to actively participate in the regeneration of cardiac and renal tissue. It is well documented that cells in the bloodstream, including immune cells, inflammatory cells and tumor cells, move in and out of tissues and organs. Furthermore, studies also demonstrate that in vivo intravascular delivery of MSC and progenitor cells “home” to the site of tubular damage. Using intravital videomicroscopy it has been shown that by three hours of injecting cells into the circulation, homing occurs by migration of the injected cells from the circulation into targeted organs. However, it is currently not possible to quantify the number of seeded cells that are retained in the targeted tissues. Likewise with in vivo seeding it is not currently feasible to determine or control untargeted sites where the infused cells may locate. Therefore, currently there is no way to control the delivery of a cell-based therapy that is administered in vivo.
Another problem associated with in vivo infusion of stem, MSC or progenitor cells is that very few blood vessels are found near the engrafted cells; this is consistent with injection into areas of ischemic damage where normal blood, flow has been interrupted. Poor blood supply has been reported to limit the growth of implanted cells and to also decrease the life-span if in fact differentiation does occur. (16)
Therefore, the in vivo delivery of stem cells by intravascular infusion is not controllable. The uniqueness of this present invention is the use of a closed-loop ex vivo perfusion system rather than an in vivo infusion. By using a closed-loop perfusion system with an acellular, near-normothermic solution the result is a controlled delivery where the cells can be tracked with the number remaining in the vascular compartment and in perfusion circuit can be quantified. It also provides the opportunity to eliminate the significant side-effects that occur with systemic administration of MSC or progenitor cell therapy. These side-effects include nausea, vomiting, diarrhea, loss of appetite, hair loss, mouth sore, ulcers, skin rashes, fatigue, reduction in red blood cells and white blood cells counts leading to susceptibility for infection and bleeding. These side-effects can persist for days post-treatment. This makes the invention an enhanced approach for not only greatly expanding the donor pool of organs for transplantation, but also for tissue-engineering and regenerative medicine as a whole.